Eugenol inhibits cell proliferation via NF-κB suppression in a rat model of gastric carcinogenesis induced by MNNG

Abstract

The modulation of intracellular nuclear factor-kappaB (NF-κB) signaling pathway involved in the deregulated expression of cell proliferation and cell cycle regulatory molecules is a pragmatic approach for chemoprevention. Eugenol (4-allyl-1-hydroxy-2-methoxybenzene), a natural phenolic constituent of oils of cloves is known to possess attractive remedial features. In the present study, we investigated the modulatory effects of eugenol on NF-κB signaling in a rat model of gastric carcinogenesis induced by N-methyl-N(')-nitro-N-nitrosoguanidine (MNNG) by analysing the expression of nuclear factor-kappaB (NF-κB) family members ((NF-κB (p50 and p65), inhibitor of kappaB alpha (IκBα), phosphorylated IκBα (p-IκBα), IκB kinase β (IKKβ)) and the NF-κB target genes that promote (e.g., cyclin D1, cyclin B and PCNA) or inhibit (e.g., p53, p21, and Gadd45) cell proliferation and cell survival. MNNG-induced gastric tumours were characterized by NF-κB activation that correlated with upregulation of IKKβ, and phosphorylation and degradation of IκBα. Furthermore, upregulation of cyclins and PCNA with downregulation of p21, p53, and Gadd45 suggested that the proliferative advantage in gastric carcinomas is dependent on elevated constitutive NF-κB activity. Administration of eugenol significantly reduced the incidence of MNNG-induced gastric tumours by suppressing NF-κB activation and modulating the expression of NF-κB target genes that regulate cell proliferation and cell survival. The targeting of NF-κB signaling pathway by eugenol may have a significant impact on chemopreventive and therapeutic approaches for cancer.

The role dietary of bioactive compounds on the regulation of histone acetylases and deacetylases: A review

“…Quercetin inhibits the expression of TNF-induced IFN--inducible protein 10 (IP-10) and macrophage inflammatory protein 2(MIP-2) related to the inhibition of p300/CBP and post-translational modifications (acetylation and phosphorylation) of H3 histones associated with the promoters of pro-inflammatory genes(Ruiz et al, 2007). Quercetin, through inhibition of HDAC and DNMT1, has also been shown to inhibit the cell cycle and induce apoptosis, thus suppressing tumor growth and angiogenesis(Priyadarsini et al, 2011).…”

<b>Anticancer activity of eugenol is not related to regulation of the oncogenic transcription factor <i>Forkhead Box M1

“…Researchers suggested that the EUGinduced apoptosis effect on cancer cell lines is related to the modulation of the Bcl-2 family proteins (Manikandan, Vinothini, Priyadarsini, Prathiba, & Nagini, 2011) and levels of p53 (Jaganathan & Supriyanto, 2012). In this regard, the literature support that increased expression of FOXM1 can downregulate the Bcl-2 family proteins and suppress the accumulation of senescence markers, such as p53 (Koo, Muir, & Lam, 2012).…”

“…It does not mean that EUG may not interfere with the FOXM1 pathway, but indicates that EUG does not downregulate the FOXM1 production. Manikandan, Vinothini, Priyadarsini, Prathiba, and Nagini (2011) investigated the EUG-induced apoptosis in gastric carcinogenesis and related the mechanism via the mitochondrial pathway by modulating the Bcl-2 family proteins (Manikandan et al, 2011). Moreover, Jaganathan and Supriyanto (2012) demonstrated that osteosarcoma cell proliferation is inhibited by EUG and that increased levels of p53, PARP, and caspase 3 cleavage accompany the EUG-induced apoptosis (Jaganathan & Supriyanto, 2012).…”

Phenylpropanoids, Eugenol Scaffold, and Its Derivatives as Anticancer

“…MNNG-induced gastric tumors were characterized by NF-κB activation that correlated with upregulation of IKKβ, and phosphorylation and degradation of IκBα. Furthermore, upregulation of cyclins and PCNA with downregulation of p21, p53, and Gadd45 suggested that the proliferative advantage in gastric carcinomas is dependent on elevated constitutive NF-κB activity [50].…”

“…Curative effect of the combination of EU and 2-methoxyestradiol on non-androgen-dependent prostate cancer. They found that this combination could effectively inhibit the proliferation of prostate cancer cells and enhance the expression of apoptosis precursor protein to prevent prostate cancer [50]. Carrasco et al [53] …”